PROJECTSUMMARY/ABSTRACT Mild cognitive impairment (MCI), dementia and stroke are substantially higher among blacks aged 45+, and among residents of the southeastern region of the US. The REasons for Geographic And Racial Differences in Stroke (REGARDS) Study is national, longitudinal cohort study of ~ 30,000 blacks and whites designed to advance the understanding of the epidemiology of cognitive decline and stroke, and the contributors to racial and geographic disparities in these outcomes. The current application has three aims: 1. Identify social, cardiovascular, and environmental mechanisms of racial and geographic disparities in incident vascular contributions to cognitive impairment and dementia (VCID). With assessment in mid-life and over a decade of longitudinal cognitive data, REGARDS is uniquely positioned to identify vascular, social, and behavioral mechanisms underlying disparities in VCID, and modifiable pathways on which interventions may narrow disparities in VCID. After completion of a nested calibration/confirmation study to develop an algorithm for the classification of MCI and dementia, we will characterize racial and geographic disparities in VCID and determine if interventions on mediators would diminish or eliminate disparities. 2. Answer as-yet-unanswered questions in stroke and cerebrovascular disease epidemiology. By continuing the successful approaches for stroke surveillance among 17000 active cohort members, the study will assess the association of risk factor changes and novel biomarkers quantified with the completion of the second in-person exam with stroke risk and disparities in stroke risk. In addition, with the aging of the cohort, this aim will provide greatly needed information on stroke epidemiology in the elderly. 3. Utilize incident risk factor data and biospecimens to identify pathways for development of incident hypertension and diabetes, with the goal of understanding the impact on incident VCID and stroke. We have documented that ?30% of the racial disparity in stroke risk is attributable to racial disparities in prevalence of hypertension and diabetes, and the study will investigate the biomarker pathways contributing to the higher incidence of hypertension and diabetes in blacks. Each proposed aim addresses a topic of profound public health impact, and REGARDS progress to date uniquely positions the study to address these aims using proven approaches in an efficient manner.